Environmental exposures may increase risk for cancer and non-cancer chronic diseases, especially among susceptible subgroups of the population. Data from completed case-control studies of risk factors for adult leukemia and kidney disease are being analyzed. Both studies included hopsital patients and population based controls. The leukemia study was conducted in connection with Cancer and Leukemia Group B, a cooperative cancer treatment group, and allowed for interviewing patients immediately following diagnosis. Other studies include risk fctors for neurodegenerative diseases as well as a study of neurobehavioral effects of pesticides. Few studies have evaluated the possible risk for adult leukemia associated with a family cancer history. Such a link can provide the impetus for further studies of specific genes and modes of inheritance. Since family history of cancer is a composite variable representing shared genes as well as exposures, family history may identify individuals with increased susceptibility due to increased likelihood of having one or more of several gene polymorphisms that are involved in cancer etiology. Cases and controls in the leukemia study provided information on cancer incidence and mortality in enumerated first and second-degree relatives and on their own exposure to known and suspected risk factors for leukemia. Relatives reported to have died since the advent of the National Death Index (NDI) were linked with that database in an attempt to validate cause of death. For those reported to have died prior to the NDI or for whom NDI matches were not found, death certificates were requested from individual states. Analyses focused on history of any cancer in any first degree relative, history of specific cancers in any first degree relative, and history of any or specific cancers in specific first degree relatives (e.g. in siblings) and on the relationship of family cancer history with risk for specific leukemia subtypes. As part of this effort, we attempted to validate reports of cancer in family members and assess the quality of such data and reported on the ability of participants to accurately report such information. We found suggestsive evindence for an association between a family history of any cancer, hematopoietic cancer, leukemia, and breast and increased leukemia risk, especially among respondents whose data collection was through a proxy because of illness or death. A family history of breast cancer in a sibling was associated with leukemia risk, regardless of interview type. We also found that persons with both a family history of breast cancer and one of several environmental risk factors (smoking, solvents, radiation) are at greater risk for leukemia than those with either one of these risk factors. In fact, for each of the exposures examined, increased risk for leukemia was observed only among persons with a family history of breast cancer. Family history of breast cancer may be a marker of susceptibility to a range of leukemia risk factors whose effects are generally weak or non-existent when considered alone. Linked population, family, and cancer registry data from Sweden will be used to evaluate the association between breast cancer and leukemia in an independent dataset. This year, we reported a weak association between alcohol consumption and leukemia risk and a risk between hair dye use and breast cancer. Beer intake was associeated with reduced risk of leukemia but wine was associated with increased risk. These different patterns may be explained by different effects of nutrients in beer and wine or differential selection by socioeconomic factors associated with alcohol intake. Hair dye results were more consistent and plausible due to the presence of known animal carcinogens in some hair dyes. The relative risk for ever use of hair dyes was 1.5 (95% confidence intercal = 1.0, 2.1). The greatest risk was observed for those usiing hair dyes for more than 15 years and/or before 1970, when dyes were more likely to contain carcinogens. A paper on leukemia risk associated with occupational exposures has been submitted. Results suggest that employment in occupations with likely exposure tosolvents is associated with increased risk. Additional analyses focusing on specific solvent and other chemical exposures and on use of medications are underway. The anaysis of data from the kidney disease study focused on lifestyle factors, kidney stones, and beverage consumption. The incidence of treated end stage kidney disease has increased steadily in the US. kidney stones may contribute to a small but signficant percentage of these cases. Our study included 548 cases with renal disfunction confirmed by hospital chart review and 514 matched population controls. Kidney stones were associated with increased risk for chronic kidney disese overall (OR 1.9, 95% CI 1.1, 3.3), diabetic nephropathy (OR=2.5, 95% CI 0.87, 7.0) and interstitial nephritis (OR 3.4, 95% CI 1.5, 7.4). Kidney stones appeared to be important largely for patients who did not have a prior history of hypertension. We also found that alcohol and smoking were not associated with risk for kidney disease in this population, although risk was increased among those consuming moonshine, a source of lead exposure in regions where moonsumption is made. Obesity significantly increased risk for developing renal disease, especially nephrosclerosis. This association appeared indepented of any relationships between obesity and hypertension, a known risk factor for kidney disease. FInally, consumption of heavy amounts of cola beverages appears associated with risk for kidney disease. This is not explained by caffeine or use of artificial sweeteners and appears to be independent of effects of glucose consumption on risk for diabetes.